Gynecologic Oncology 136 (2015) 413–414
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Editorial
Symptom management of gynecologic cancers: Refocusing on the forest
Curing gynecologic cancers and improving survival have always been the drivers of research endeavors in gynecologic oncology. New combinations of drugs, adding radiation therapy, and investigating new, targeted therapies have all been, at the core, attempts to prolong survival or progression and prevent recurrence. Although noble efforts and certainly the prize we must keep our eyes on, these trials rarely inform us of how to help the women we see daily who are suffering from the effects of their cancer as well as the side effects of the therapies we provide. By focusing on the trees of cure, we often lose sight of the forest of symptoms that accompany these tumors. Managing the symptoms of cancer and cancer therapies is a vast and nascent topic, and one that is vital to providing quality care for women with gynecologic cancer. In an effort to highlight the work being done in this area, a portion of this special issue of Gynecologic Oncology has been devoted to the research of symptom management in gynecologic cancers. It is estimated that over 90,000 women will be diagnosed with a gynecologic cancer in the United States in 2014 [1]. With improvements in early detection and new therapies, many will survive their cancer diagnosis. Others may have significant survival extension with maintenance therapy. As these possibilities emerge, the persistent symptoms of cancer and the symptomatic sequelae of treatment become of increasing concern for the maintenance or resumption of function. Gynecologic cancer patients experience a wide range of symptoms including nausea, anorexia, vomiting, bowel obstruction, sexual dysfunction, abdominal bloating, fatigue, pain, neuropathy, alopecia, treatment-related cognitive impairment and depression. In addition, cancer or the treatment of cancer can reduce fertility, induce menopause and significantly impair sexual function. Many of these cancers and treatments may induce multiple symptoms at different time points in the course of treatment and recovery. Accurate measurement of these symptoms can be difficult due to the interplay of co-morbidities, complex treatments and disease severity. However, patient reported outcomes, standardized multiple symptom assessment measures, and health related quality of life (HRQOL) measures are now considered standard measurements for any new clinical trial in order to measure the impact of the therapies on daily activities and quality of life. Evidence of the importance of symptom management can be seen in a growing body of literature, such as the recent report from Havrilesky and colleagues [2]. They found that women with advanced or recurrent ovarian cancer were willing to accept significant losses in progression free survival to reduce severe side effects of nausea and vomiting, neuropathy and abdominal symptoms. It is of great significance when a major oncology journal recognizes the importance of disease- and treatment-related symptom assessment and management in oncology care. To prepare this special issue, a solicitation was made for abstracts related to the broad topic of symptom
http://dx.doi.org/10.1016/j.ygyno.2015.01.555 0090-8258/© 2015 Elsevier Inc. All rights reserved.
management. Ninety abstracts were received and 18 were invited to submit manuscripts for consideration. We attempted to select articles of high scientific merit that covered a broad range of symptom management topics including perioperative issues, palliative care, neuropathy and fatigue. Where topics were lacking, we invited review articles from leaders in the field, including a review of cancer- and treatmentrelated fatigue and therapy-induced neuropathy. Manuscripts were selected following the standard peer review process for the journal. Several of the papers in this collection deal with the potential integration of symptom management or palliative care to daily practice for those who manage gynecologic cancers. Despite the increasing emphasis of the high-priority of symptom assessment and management, systematic reviews continue to indicate that pain and other symptoms associated with cancer and its treatment are not optimally controlled [3]. Many patients with more advanced cancer remain highly symptomatic, and many of these symptoms are the results of aggressive therapy. There is a large literature that suggests that lack of symptom assessment and lack of rapid symptom intervention in clinical encounters may be responsible for the substantial under-treatment of symptoms, especially pain, in cancer patients. Kirchheiner et al. longitudinally studied a group of women with locally advanced cervical cancer receiving chemoradiation, and compared their reported responses with the normative group of similarly aged women [4]. As expected, aggressive therapy was associated with the dramatic increase in symptoms as well as decreases in several rated dimensions of quality of life. Symptom severity tended to return to baseline levels at three months, but ratings of general health and functioning remained impaired. They suggest in conclusion that patients be counseled prior to these therapies about the frequency and intensity of symptoms they will experience as well as the expected time of recovery. More aggressive symptom management may provide significant relief in a timely manner. Lefkowits et al. studied symptom burden before and one day after palliative care consult in hospitalized gynecologic patients [5]. This study was a single institution, prospective, observational study with no control group. A variety of symptoms were rated for severity at the time of consultation by palliative care as well as on the following day and at discharge. They found a dramatic reduction (50% or greater) in severe pain, anorexia, fatigue and nausea. Many of these referrals for symptomatic management were made on the day of admission or the day after, while others received a palliative care referral at time of discharge. Symptom improvement was noted following the consult whenever made, suggesting that early recognition and treatment of symptoms may benefit patients. Although asking patients to rate pain has become a routine part of patient care, pain is often not the most bothersome symptom to
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Editorial
patients. Proposed quality of oncologic care standards endorse the assessment of multiple symptoms [6]. Meeting this need is often seen as time intensive and complicating hospital care and consultations. As illustrated in the review by Gilbert et al. and the pilot study by Meyer et al., symptom assessment can be done routinely and efficiently with the use of simple patient reported outcome measures, and with the use of increasingly available technology [7,8]. The first step is to select a brief patient rated scale that takes little time to administer. Gilbert suggests gynecologic disease-specific versions of the EORTC-measures or the FACT system (FACT-G), while Meyer uses a disease-specific version of the MD Anderson Symptom Inventory. The main factor in tool selection, as Gilbert et al. point out, is that the data obtained be easily understood by both patients and clinicians, and that issues in need of attention are rapidly identified for clinical attention. Patients can respond to these questionnaires between clinic visits on computers, telephone– computer interfaces, or smart phones, and these data can be gathered in hospital or clinic using tablet computers. With new guidelines and the increase in the demand for patient report in quality of life assessment and clinical trials, we are likely to see a larger role for patient reported outcomes in the future. A significant issue is that these additional data need to be “filtered” for the clinical encounter, and this can be done through electronic health record systems. Many patients are relatively symptom free, or have symptom severity levels that don't require intervention. For instance, “alerts” based on symptom level of severity that mark the need for intervention are beginning to be explored [5,7]. Among the most frequent symptoms likely to be reported by gynecologic patients in treatment are fatigue and neuropathy. This issue presents reviews of the current status of each of these symptoms. Some progress is being made in understanding the biologic mechanism of fatigue and chemotherapy induced peripheral neuropathy (CIPN), and both chapters suggest some treatment options for patients that might be offered for patients who are distressed by these symptoms [9,10]. At this point, there are no approved agents to prevent either of these symptoms, and the need for additional research understanding both of these symptoms may lead to more tailored ways to alleviate them. A discussion of patient symptoms in gynecologic oncology must include perioperative pain control, and new surgical techniques often change the nature of post-operative pain. Hotujec and colleagues performed a randomized, controlled trial on the use of transversus abdominis plane (TAP) block to alleviate postoperative pain from the larger assistant port sites used in robotic surgery [11]. While TAP block did not reduce opiate use in this trial, the data from the trial did illuminate discrepancies in opiate need for elderly patients. Their article endorses a nomogram for opiate use in elderly patients based on this data. Another symptom faced all too often by women with gynecologic cancer is the malignant ascites. Ascites can cause pain, bloating and difficulty eating which can contribute to poor nutrition and fatigue. The risks of repeated paracenteses as well as nutritional sequelae can impact perioperative care as well as chemotherapy administration. Stukan et al. reported on the use of a 14 gauge vascular catheter, placed in the outpatient setting for alleviating the symptoms of malignant ascites and lymphocysts. They report improved preoperative nutritional intake with the use of the catheter, and show that it is a safe and effective alternative to repeat paracentesis [12]. In addition, Walter and colleagues report on the performance of prognostic indices in patients with central nervous system (CNS) metastases from gynecologic malignancies. The data collected from this cohort of patients provides us with additional insight into the nature of CNS metastasis in gynecologic cancer and highlights the importance of a multi-disciplinary approach to treatment [13]. It is obvious that sexual concerns, concerns about intimacy, and specific symptoms related to gynecologic disease are management issues of
high import to our patients, and Maguire, et al. present a systematic review of supportive care needs in cervical cancer [14]. They underline the chronic psychological distress reported by these patients, especially with fears of recurrence, loss of intimacy and embarrassment. They point out that few interventions have been proposed to meet these needs, especially the need for more information and psychological support, coupled with the pressing need for more research on how best to provide these services. As research continues to reveal the sexual/intimacy concerns of gynecologic cancer survivors, groups such as the Scientific Network on Female Sexual Health and Cancer will help guide the research and treatment guidelines for women facing such issues. This special issue is a tremendous first step in highlighting the work being done in symptom management of gynecologic cancers. We hope that the articles may help us better counsel and treat women with gynecologic cancer and serve as a strong foundation for future research. References [1] ACS. Cancer Facts and Figs. 2014. Atlanta: American Cancer Society; 2014. [2] Havrilesky LJ, Alvarez Secord A, Ehrisman JA, Berchuck A, Valea FA, Lee PS, et al. Patient preferences in advanced or recurrent ovarian cancer. Cancer 2014;120:3651–9. [3] Greco MT, Roberto A, Corli O, Deandrea S, Bandieri E, Cavuto S, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014;32:4149–54. [4] Kirchheiner K, Nout RA, Czajka-Pepl A, Ponocny-Seliger E, Sturdza AE, Dimopoulos JC, et al. Health related quality of life and patient reported symptoms before and during definitive radio(chemo)therapy using image-guided adaptive brachytherapy for locally advanced cervical cancer and early recovery — a mono-institutional prospective study. Gynecol Oncol 2015;136:415–23 [in this issue]. [5] Lefkowits C, Teuteberg W, Courtney-Brooks M, Sukumvanich P, Ruskin R, Kelley JL. Improvement in symptom burden within one day after palliative care consultation in a cohort of gynecologic oncology inpatients. Gynecol Oncol 2015;136:424–8 [in this issue]. [6] Hassett MJ, McNiff KK, Dicker AP, Gilligan T, Hendricks CB, Lennes I, et al. Highpriority topics for cancer quality measure development: results of the 2012 American Society of Clinical Oncology Collaborative Cancer Measure Summit. J Oncol Pract, vol. 10. American Society of Clinical Oncology; 2014. p. e160–6. [7] Gilbert A, Sebag-Montefiore D, Davidson S, Velikova G. Use of patient-reported outcomes to measure symptoms and health related quality of life in the clinic. Gynecol Oncol 2015;136:429–39 [in this issue]. [8] Meyer LA, Nick AM, Shi Q, Wang XS, Williams L, Brock T, et al. Perioperative trajectory of patient reported symptoms: a pilot study in gynecologic oncology patients. Gynecol Oncol 2015;136:440–5 [in this issue]. [9] Wang XS, Woodruff JF. Cancer-related and treatment-related fatigue. Gynecol Oncol 2015;136:446–52 [in this issue]. [10] Kim JH, Dougherty PM, Abdi S. Basic science and clinical management of painful and non-painful chemotherapy-related neuropathy. Gynecol Oncol 2015;136:453–9 [in this issue]. [11] Hotujec BT, Spencer RJ, Donnelly MJ, Bruggink SM, Rose SL, Al-Niaimi A, et al. Transversus abdominis plane block in robotic gynecologic oncology: a randomized, placebo-controlled trial. Gynecol Oncol 2015;136:460–5 [in this issue]. [12] Stukan M, Leśniewski-Kmak K, Wróblewska M, Dudziak M. Management of symptomatic ascites and post-operative lymphocysts with an easy-to-use, patientcontrolled, vascular catheter. Gynecol Oncol 2015;136:466–71 (in this issue). [13] Walter AC, Gunderson CC, Vesely SK, Algan O, Sughrue M, Slaughter KN, et al. Central nervous system metastasis in gynecologic cancer: symptom management, prognosis and palliative management strategies. Gynecol Oncol 2015;136:472–7 [in this issue]. [14] Maguire R, Kotronoulas G, Simpson M, Paterson C. A systematic review of the supportive care needs of women living with and beyond cervical cancer. Gynecol Oncol 2015;136:478–90 [in this issue].
Charles S. Cleeland Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Stephen L. Rose Division of Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA Corresponding author. E-mail address: [email protected].
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Editorial
Symptom management of gynecologic cancers: Refocusing on the forest
Curing gynecologic cancers and improving survival have always been the drivers of research endeavors in gynecologic oncology. New combinations of drugs, adding radiation therapy, and investigating new, targeted therapies have all been, at the core, attempts to prolong survival or progression and prevent recurrence. Although noble efforts and certainly the prize we must keep our eyes on, these trials rarely inform us of how to help the women we see daily who are suffering from the effects of their cancer as well as the side effects of the therapies we provide. By focusing on the trees of cure, we often lose sight of the forest of symptoms that accompany these tumors. Managing the symptoms of cancer and cancer therapies is a vast and nascent topic, and one that is vital to providing quality care for women with gynecologic cancer. In an effort to highlight the work being done in this area, a portion of this special issue of Gynecologic Oncology has been devoted to the research of symptom management in gynecologic cancers. It is estimated that over 90,000 women will be diagnosed with a gynecologic cancer in the United States in 2014 [1]. With improvements in early detection and new therapies, many will survive their cancer diagnosis. Others may have significant survival extension with maintenance therapy. As these possibilities emerge, the persistent symptoms of cancer and the symptomatic sequelae of treatment become of increasing concern for the maintenance or resumption of function. Gynecologic cancer patients experience a wide range of symptoms including nausea, anorexia, vomiting, bowel obstruction, sexual dysfunction, abdominal bloating, fatigue, pain, neuropathy, alopecia, treatment-related cognitive impairment and depression. In addition, cancer or the treatment of cancer can reduce fertility, induce menopause and significantly impair sexual function. Many of these cancers and treatments may induce multiple symptoms at different time points in the course of treatment and recovery. Accurate measurement of these symptoms can be difficult due to the interplay of co-morbidities, complex treatments and disease severity. However, patient reported outcomes, standardized multiple symptom assessment measures, and health related quality of life (HRQOL) measures are now considered standard measurements for any new clinical trial in order to measure the impact of the therapies on daily activities and quality of life. Evidence of the importance of symptom management can be seen in a growing body of literature, such as the recent report from Havrilesky and colleagues [2]. They found that women with advanced or recurrent ovarian cancer were willing to accept significant losses in progression free survival to reduce severe side effects of nausea and vomiting, neuropathy and abdominal symptoms. It is of great significance when a major oncology journal recognizes the importance of disease- and treatment-related symptom assessment and management in oncology care. To prepare this special issue, a solicitation was made for abstracts related to the broad topic of symptom
http://dx.doi.org/10.1016/j.ygyno.2015.01.555 0090-8258/© 2015 Elsevier Inc. All rights reserved.
management. Ninety abstracts were received and 18 were invited to submit manuscripts for consideration. We attempted to select articles of high scientific merit that covered a broad range of symptom management topics including perioperative issues, palliative care, neuropathy and fatigue. Where topics were lacking, we invited review articles from leaders in the field, including a review of cancer- and treatmentrelated fatigue and therapy-induced neuropathy. Manuscripts were selected following the standard peer review process for the journal. Several of the papers in this collection deal with the potential integration of symptom management or palliative care to daily practice for those who manage gynecologic cancers. Despite the increasing emphasis of the high-priority of symptom assessment and management, systematic reviews continue to indicate that pain and other symptoms associated with cancer and its treatment are not optimally controlled [3]. Many patients with more advanced cancer remain highly symptomatic, and many of these symptoms are the results of aggressive therapy. There is a large literature that suggests that lack of symptom assessment and lack of rapid symptom intervention in clinical encounters may be responsible for the substantial under-treatment of symptoms, especially pain, in cancer patients. Kirchheiner et al. longitudinally studied a group of women with locally advanced cervical cancer receiving chemoradiation, and compared their reported responses with the normative group of similarly aged women [4]. As expected, aggressive therapy was associated with the dramatic increase in symptoms as well as decreases in several rated dimensions of quality of life. Symptom severity tended to return to baseline levels at three months, but ratings of general health and functioning remained impaired. They suggest in conclusion that patients be counseled prior to these therapies about the frequency and intensity of symptoms they will experience as well as the expected time of recovery. More aggressive symptom management may provide significant relief in a timely manner. Lefkowits et al. studied symptom burden before and one day after palliative care consult in hospitalized gynecologic patients [5]. This study was a single institution, prospective, observational study with no control group. A variety of symptoms were rated for severity at the time of consultation by palliative care as well as on the following day and at discharge. They found a dramatic reduction (50% or greater) in severe pain, anorexia, fatigue and nausea. Many of these referrals for symptomatic management were made on the day of admission or the day after, while others received a palliative care referral at time of discharge. Symptom improvement was noted following the consult whenever made, suggesting that early recognition and treatment of symptoms may benefit patients. Although asking patients to rate pain has become a routine part of patient care, pain is often not the most bothersome symptom to
414
Editorial
patients. Proposed quality of oncologic care standards endorse the assessment of multiple symptoms [6]. Meeting this need is often seen as time intensive and complicating hospital care and consultations. As illustrated in the review by Gilbert et al. and the pilot study by Meyer et al., symptom assessment can be done routinely and efficiently with the use of simple patient reported outcome measures, and with the use of increasingly available technology [7,8]. The first step is to select a brief patient rated scale that takes little time to administer. Gilbert suggests gynecologic disease-specific versions of the EORTC-measures or the FACT system (FACT-G), while Meyer uses a disease-specific version of the MD Anderson Symptom Inventory. The main factor in tool selection, as Gilbert et al. point out, is that the data obtained be easily understood by both patients and clinicians, and that issues in need of attention are rapidly identified for clinical attention. Patients can respond to these questionnaires between clinic visits on computers, telephone– computer interfaces, or smart phones, and these data can be gathered in hospital or clinic using tablet computers. With new guidelines and the increase in the demand for patient report in quality of life assessment and clinical trials, we are likely to see a larger role for patient reported outcomes in the future. A significant issue is that these additional data need to be “filtered” for the clinical encounter, and this can be done through electronic health record systems. Many patients are relatively symptom free, or have symptom severity levels that don't require intervention. For instance, “alerts” based on symptom level of severity that mark the need for intervention are beginning to be explored [5,7]. Among the most frequent symptoms likely to be reported by gynecologic patients in treatment are fatigue and neuropathy. This issue presents reviews of the current status of each of these symptoms. Some progress is being made in understanding the biologic mechanism of fatigue and chemotherapy induced peripheral neuropathy (CIPN), and both chapters suggest some treatment options for patients that might be offered for patients who are distressed by these symptoms [9,10]. At this point, there are no approved agents to prevent either of these symptoms, and the need for additional research understanding both of these symptoms may lead to more tailored ways to alleviate them. A discussion of patient symptoms in gynecologic oncology must include perioperative pain control, and new surgical techniques often change the nature of post-operative pain. Hotujec and colleagues performed a randomized, controlled trial on the use of transversus abdominis plane (TAP) block to alleviate postoperative pain from the larger assistant port sites used in robotic surgery [11]. While TAP block did not reduce opiate use in this trial, the data from the trial did illuminate discrepancies in opiate need for elderly patients. Their article endorses a nomogram for opiate use in elderly patients based on this data. Another symptom faced all too often by women with gynecologic cancer is the malignant ascites. Ascites can cause pain, bloating and difficulty eating which can contribute to poor nutrition and fatigue. The risks of repeated paracenteses as well as nutritional sequelae can impact perioperative care as well as chemotherapy administration. Stukan et al. reported on the use of a 14 gauge vascular catheter, placed in the outpatient setting for alleviating the symptoms of malignant ascites and lymphocysts. They report improved preoperative nutritional intake with the use of the catheter, and show that it is a safe and effective alternative to repeat paracentesis [12]. In addition, Walter and colleagues report on the performance of prognostic indices in patients with central nervous system (CNS) metastases from gynecologic malignancies. The data collected from this cohort of patients provides us with additional insight into the nature of CNS metastasis in gynecologic cancer and highlights the importance of a multi-disciplinary approach to treatment [13]. It is obvious that sexual concerns, concerns about intimacy, and specific symptoms related to gynecologic disease are management issues of
high import to our patients, and Maguire, et al. present a systematic review of supportive care needs in cervical cancer [14]. They underline the chronic psychological distress reported by these patients, especially with fears of recurrence, loss of intimacy and embarrassment. They point out that few interventions have been proposed to meet these needs, especially the need for more information and psychological support, coupled with the pressing need for more research on how best to provide these services. As research continues to reveal the sexual/intimacy concerns of gynecologic cancer survivors, groups such as the Scientific Network on Female Sexual Health and Cancer will help guide the research and treatment guidelines for women facing such issues. This special issue is a tremendous first step in highlighting the work being done in symptom management of gynecologic cancers. We hope that the articles may help us better counsel and treat women with gynecologic cancer and serve as a strong foundation for future research. References [1] ACS. Cancer Facts and Figs. 2014. Atlanta: American Cancer Society; 2014. [2] Havrilesky LJ, Alvarez Secord A, Ehrisman JA, Berchuck A, Valea FA, Lee PS, et al. Patient preferences in advanced or recurrent ovarian cancer. Cancer 2014;120:3651–9. [3] Greco MT, Roberto A, Corli O, Deandrea S, Bandieri E, Cavuto S, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014;32:4149–54. [4] Kirchheiner K, Nout RA, Czajka-Pepl A, Ponocny-Seliger E, Sturdza AE, Dimopoulos JC, et al. Health related quality of life and patient reported symptoms before and during definitive radio(chemo)therapy using image-guided adaptive brachytherapy for locally advanced cervical cancer and early recovery — a mono-institutional prospective study. Gynecol Oncol 2015;136:415–23 [in this issue]. [5] Lefkowits C, Teuteberg W, Courtney-Brooks M, Sukumvanich P, Ruskin R, Kelley JL. Improvement in symptom burden within one day after palliative care consultation in a cohort of gynecologic oncology inpatients. Gynecol Oncol 2015;136:424–8 [in this issue]. [6] Hassett MJ, McNiff KK, Dicker AP, Gilligan T, Hendricks CB, Lennes I, et al. Highpriority topics for cancer quality measure development: results of the 2012 American Society of Clinical Oncology Collaborative Cancer Measure Summit. J Oncol Pract, vol. 10. American Society of Clinical Oncology; 2014. p. e160–6. [7] Gilbert A, Sebag-Montefiore D, Davidson S, Velikova G. Use of patient-reported outcomes to measure symptoms and health related quality of life in the clinic. Gynecol Oncol 2015;136:429–39 [in this issue]. [8] Meyer LA, Nick AM, Shi Q, Wang XS, Williams L, Brock T, et al. Perioperative trajectory of patient reported symptoms: a pilot study in gynecologic oncology patients. Gynecol Oncol 2015;136:440–5 [in this issue]. [9] Wang XS, Woodruff JF. Cancer-related and treatment-related fatigue. Gynecol Oncol 2015;136:446–52 [in this issue]. [10] Kim JH, Dougherty PM, Abdi S. Basic science and clinical management of painful and non-painful chemotherapy-related neuropathy. Gynecol Oncol 2015;136:453–9 [in this issue]. [11] Hotujec BT, Spencer RJ, Donnelly MJ, Bruggink SM, Rose SL, Al-Niaimi A, et al. Transversus abdominis plane block in robotic gynecologic oncology: a randomized, placebo-controlled trial. Gynecol Oncol 2015;136:460–5 [in this issue]. [12] Stukan M, Leśniewski-Kmak K, Wróblewska M, Dudziak M. Management of symptomatic ascites and post-operative lymphocysts with an easy-to-use, patientcontrolled, vascular catheter. Gynecol Oncol 2015;136:466–71 (in this issue). [13] Walter AC, Gunderson CC, Vesely SK, Algan O, Sughrue M, Slaughter KN, et al. Central nervous system metastasis in gynecologic cancer: symptom management, prognosis and palliative management strategies. Gynecol Oncol 2015;136:472–7 [in this issue]. [14] Maguire R, Kotronoulas G, Simpson M, Paterson C. A systematic review of the supportive care needs of women living with and beyond cervical cancer. Gynecol Oncol 2015;136:478–90 [in this issue].
Charles S. Cleeland Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Stephen L. Rose Division of Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA Corresponding author. E-mail address: [email protected].
